COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation.

COL1A1::PDGFB fusion uterine sarcoma is a rare uterine mesenchymal tumor with some clinicopathological features that overlap with those of soft tissue dermatofibrosarcoma protuberans. However, the varied clinicopathologic and genetic characteristics have not been fully revealed, which may be a potential pitfall for diagnosis. Here, we present a case of COL1A1::PDGFB fusion-positive uterine sarcoma in a 49-years-old female. Histologically, the tumor from the initial marginal excision predominantly exhibited high-grade fibrosarcomatous and myxofibrosarcoma-like appearances, while a low-grade focal area displaying storiform growth was identified in the residual tumor after subsequently extended resection. Immunohistochemically, the high-grade components mainly exhibited focal positivity for CD34 and mutated-type p53 immunoreactivity, whereas the low-grade component showed diffuse positivity for CD34 and wild-type p53 staining. The COL1A1::PDGFB fusion was confirmed by fluorescence in situ hybridization and next-generation sequencing. In addition, the TERT-124 C > T mutation was further identified in this lesion's fibrosarcomatous and classic storiform components. To the best of our knowledge, this is the first described case of COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation, which might be a novel genetic finding associated with tumorigenesis of this rare tumor.

ALK-rearranged, CD34-positive spindle cell neoplasms resembling dermatofibrosarcoma protuberans: a study of seven cases.

AIMS: The majority of dermatofibrosarcoma protuberans (DFSP) harbour PDGFB or PDGFD rearrangements. We encountered ALK expression/rearrangement in a PDGFB/D-negative CD34-positive spindle cell neoplasm with features similar to DFSP, prompting evaluation of ALK-rearrangements in DFSP and plaque-like CD34-positive dermal fibroma (P-LDF). METHODS AND RESULTS: We searched the archives of academic institutions for cases previously coded as DFSP and P-LDF. NGS-naïve or PDGFB-negative DFSP were screened for ALK (clone D5F3) expression by immunohistochemistry. NGS or ALK FISH was performed on ALK-positive cases. Methylome profiling studies were performed and compared with conventional DFSP. One case of "DFSP" and two "P-LDF" with ALK expression were identified from the archives, while four cases were detected prospectively. These seven cases (6F:1M; 8 months to 76 years) arose in the dermis of the arm (two), scalp, eyelid, thigh, abdomen, and shoulder and ranged from 0.4 to 4.2 cm. Tumours were composed of spindled cells and displayed a storiform growth pattern. Cytologic atypia was absent, and mitotic figures were scarce (0-2/10 HPFs, high power fields). The lesional cells were diffusely positive for CD34 and ALK and negative for S100 protein. By NGS (n = 5), ALK fusion partners included DCTN1 (2), PLEKHH2, and CLIP2 in DFSP-like cases and FLNA in P-LDF-like lesions. ALK FISH was positive in one (of two) cases previously labelled P-LDF. Methylome profiling of two (of three) ALK-rearranged DFSP-like tumours showed clustering with conventional DFSP in the UMAP dimension reduction plot. To date, no tumour has recurred (n = 2; 26, 27 months). CONCLUSION: We describe a cohort of novel ALK-rearranged tumours with morphologic features similar to DFSP.

Cellular and molecular landscape of primary dermatofibrosarcoma protuberans: Insights from single-cell RNA sequencing analysis.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma characterized by the COL1A1-PDGFB fusion gene. This study utilized single-cell RNA sequencing to dissect the cellular and molecular landscape of primary DFSP. Distinct DFSP cell clusters, exhibiting fibroblast-like traits, revealed variations in pathways associated with proliferation, inflammation and metabolism. Differential gene expression analysis during the differentiation from tumour stem cells to DFSP cells unveiled SMOC2, DCN and TGFBR3 as potential regulators of tumour invasion and immune infiltration through VEGF/TGF-ß signalling modulation. Cellular communication analysis highlighted interactions within DFSP cell clusters and with endothelial cells, implicating molecules such as NAMPT, ANGPT2 and PTN in pathogenesis and treatment resistance. These findings offer insights into DFSP intratumour heterogeneity, elucidate molecular mechanisms underlying tumour behaviour, and suggest potential therapeutic targets.

Conventional and contrast-enhanced ultrasound in the differential diagnosis of recurrent dermatofibrosarcoma protuberans and postoperative scar.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) has a high recurrence rate after resection. Because of the lack of specific manifestations, recurrent DFSP is easily misdiagnosed as post-resection scar. A few series have reported ultrasound findings of recurrent DFSP; moreover, the usefulness of contrast-enhanced ultrasound in differentiating recurrent DFSP has not been studied. OBJECTIVE: We investigated conventional and contrast-enhanced ultrasound in the differential diagnosis of recurrent DFSP and post-resection scar. METHODS: We retrospectively evaluated the findings of conventional and contrast-enhanced ultrasound in 34 cases of recurrent DFSP and 38 postoperative scars examined between January 2018 and December 2022. RESULTS: The depth and vascular density of recurrent DFSP were greater than those of postoperative scars (P < 0.05). On gray-scale ultrasound, recurrent DFSP lesions were more commonly irregular, heterogeneous, and hypoechoic, with finger-like projections and ill-defined borders. Postoperative scar was more likely to appear as hypoechoic and homogeneous with well-defined borders (P < 0.05). On color Doppler ultrasound, recurrent DFSP was more likely to feature rich arterial and venous blood flow, and postoperative scar was more likely to display poor blood flow (P < 0.05). On contrast-enhanced ultrasound, recurrent DFSP was more likely to feature heterogeneous hyper-enhancement, and postoperative scar was more likely to display homogeneous iso-enhancement (P < 0.05). Recurrent DFSP presented a higher peak and sharpness than postoperative scar (P < 0.05). CONCLUSION: Conventional and contrast-enhanced ultrasound produced distinct features of recurrent DFSP and post-resection scar, which could improve the accuracy of differential diagnosis.

Survival outcomes of rare cutaneous malignancies within an insured cohort of patients, 1988-2018.

BACKGROUND: There are limited survival data on cutaneous angiosarcoma (CAS), dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC). OBJECTIVE: To analyze survival trends in CAS, DFSP, MCC, and SC among a racially diverse, insured cohort of patients. METHODS: Using data from the Kaiser Permanente Southern California Cancer Registry, we identified adults diagnosed with CAS, DFSP, MCC, or SC between January 1, 1988 and December 31 2018, followed through December 31, 2021. RESULTS: Our cohort consisted of 83 diagnoses of CAS, 490 diagnoses of DFSP, 411 diagnoses of MCC, and 249 diagnoses of SC. Our analysis revealed no significant differences in overall or disease-specific 1000 person-years mortality rates among our populations of non-Hispanic Whites, Hispanics, African American/Blacks, and Asian American/Pacific Islanders diagnosed with CAS, DFSP, MCC, or SC. On multivariate analysis, controlling for patient and tumor characteristics, there was similarly no increased risk of overall mortality for minorities diagnosed with CAS, DFSP, MCC, or SC. LIMITATIONS: Retrospective nature of the analysis and small sample size. CONCLUSION: Contrary to existing literature, our results show a notable lack of racially driven survival disparities among insured individuals with CAS, DFSP, MCC, and SC, emphasizing the importance of health care coverage.

An unusual presentation of dermatofibrosarcoma protuberans: A case of fibrosarcomatous dermatofibrosarcoma protuberans with pleomorphic angiectatic tumor-like changes.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive superficial mesenchymal neoplasm characterized by monomorphic spindle-cell proliferation with a storiform pattern. It can demonstrate pigmentation, myxoid changes, myoid differentiation, plaque-like growth, and fibrosarcomatous features; its varied presentation often complicates diagnosis. We report an extremely rare case of fibrosarcomatous DFSP with features reminiscent of a pleomorphic hyalinizing angiectatic tumor (PHAT) in a 73-year-old male. The diagnosis was confirmed using a reverse transcription polymerase chain reaction. To the best of our knowledge, PHAT-like changes in DFPS have not been described so far. Therefore, this report provides a novel variant of DFSP and expands the differential diagnosis of DFSP and PHAT.

A cutaneous spindle cell neoplasm characterized by a COL3A1::PDGFRA fusion.

Cutaneous spindle cell neoplasms can be challenging to diagnose using routine histopathological techniques alone, and the growing repertoire of molecular studies can assist in diagnosis. We describe a cutaneous spindle cell neoplasm characterized by a COL3A1::PDGFRA rearrangement predicted to lead to constitutive activation of the PDGFRA kinase domain. The lesion shows some similarities to dermatofibrosarcoma protuberans and also benign and epithelioid fibrous histiocytomas but is distinct from these entities histopathologically and molecularly. This tumor is considered to represent an entity in the spectrum of PDGFR-driven cutaneous mesenchymal neoplasms.

A study of collagen refractility in dermatofibroma and dermatofibrosarcoma protuberans using diffractive microscopy.

BACKGROUND: Diffractive microscopy creates contrast within samples that are otherwise uniform under bright light. This technique can highlight subtle differences in refractive indices within birefringent samples containing varying amounts of mature collagen. Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) possess differences in their mature collagen content and, therefore, may be distinguishable using diffractive microscopy. METHODS: Two hundred forty-two DF and 85 DFSP hematoxylin-eosin (H&E)-stained specimens were analyzed using diffractive microscopy. Data regarding the distribution pattern and strength of refractility was recorded. RESULTS: DFSP was more frequently found to be focally, weakly, or non-refractile (82.9%; n = 68) under diffractive microscopy, while DF more often showed diffusely bright refractility (52.9%; n = 128). DFSP samples with diffuse refractility in portions of the lesion (17.1%; n = 14) also exhibited a unique checkerboard pattern distinct from that which was seen in DF samples. CONCLUSIONS: The absence of diffuse refractility was more closely associated with DFSP, as was the presence of a unique checkerboard diffraction pattern. Despite high sensitivity (Sn = 82.9%), absent refractility was not a specific test (Sp = 52.9%), with 47.1% (n = 114) of DF samples sharing this feature. The distinction between DF and DFSP is often diagnosed using H&E alone. In difficult cases, examination of collagen under diffractive microscopy may be useful in distinguishing DFSP from DF and provide an alternative cost-effective tool to immunohistochemical staining.

Multiple primary dermatofibrosarcoma protuberans tumors in a single patient with chromosomal microarray analysis: A case report and review.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with a high propensity for local invasion and recurrence. Although it is a rare event, the occurrence of multiple tumors in a single patient raises a diagnostic dilemma, as metastatic disease should be differentiated from multiple primary malignant events. In more than 90% of DFSP, a pathogenic t(17;22) translocation leads to the expression of COL1A1::PDGFB fusion transcripts. Karyotype analysis, fluorescence in situ hybridization, and RT-PCR can be useful ancillary studies in detecting this characteristic rearrangement, and sequencing of the fusion transcript can be used to support a clonal origin in metastatic and multifocal disease. However, previous reports have demonstrated variable sensitivity of these assays, in part due to the high sequence variability of the COL1A1::PDGFB fusion. Here, we report a patient who developed two distinct DFSP tumors over the course of 7 years. Chromosomal microarray analysis identified distinctive genomic alterations in the two tumors, supporting the occurrence of multiple primary malignant events.

Dermatofibrosarcoma Protuberans: A Study of 148 Patients.

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is the most common sarcoma of the skin. Although distant metastases are infrequent, DFSP is highly aggressive locally with frequent local recurrences. It has been reported that the presence within the tumour of areas histopathologically mimicking fibrosarcoma may increase the risk of recurrence. OBJECTIVE: The objective of this study was to review the clinical features of our patients with DFSP and the factors associated with recurrence of the tumour, focussing on the presence of fibrosarcomatous areas. METHODS: Retrospective study of patients with DFSP diagnosed in 1990-2021 in a tertiary university hospital. The medical records were reviewed to obtain the following data: age, sex, tumour location, diameter, evolution time, presence of fibrosarcomatous areas, development of recurrence, and follow-up. Factors possibly associated with disease-free survival were analysed with Kaplan-Meier method and multivariate Cox regression. RESULTS: 148 patients (74 women/74 men, mean age 46.28 years, SD 14.431) were included in the study. Tumours involved the head and neck in 15 cases, thorax in 31, abdomen in 16, upper back in 43, lower back in 10, upper extremities in 10, and lower extremities in 23. Fibrosarcoma-like areas were observed in 16 tumours (10.81%). In 17 patients (11.49%), recurrences were observed (13 local recurrences, 3 lung metastasis, and 1 local recurrence with lung metastasis). Fibrosarcomatous DFSP recurred more frequently than classic DFSP (50% vs. 6.82%, respectively), and its disease-free survival was significantly lower (p < 0.001). In multivariate Cox regression, the presence of fibrosarcomatous areas was the only factor influencing disease-free survival. CONCLUSIONS: It is important to identify the fibrosarcomatous variant since it recurs more frequently and has lower recurrence-free survival. Distant metastases, mainly in the lung, are also more frequent in fibrosarcomatous DFSP.

Integrating vascularity into the pattern classification of pilomatricomas on ultrasound provides a more competent approach for discriminative evaluation.

BACKGROUND: Pilomatricoma has various manifestations on color Doppler ultrasound, and a differential diagnosis is challenging. The objective of this study was to investigate which characteristics of skin lesions on color Doppler ultrasound are effective in distinguishing pilomatricoma from epidermoid cyst and dermatofibrosarcoma protuberans. MATERIALS AND METHODS: Records of patients with pilomatricomas (n = 63), epidermoid cysts (n = 76), and dermatofibrosarcoma protuberans (n = 19) who underwent color Doppler ultrasound evaluation and surgical excision were reviewed. The anatomical distribution and color Doppler ultrasound characteristics of these lesions were analyzed. The 63 pilomatricomas were categorized into five types based on their color Doppler ultrasound characteristics, and the roles of these five types in the differential diagnosis of the aforementioned diseases were studied. RESULTS: Pilomatricomas, epidermoid cysts, and dermatofibrosarcoma protuberans exhibited some similar characteristics. Dominantly markedly hyperechoic or hyperechoic appearance, posterior acoustic shadowing, and the presence of vascularity were the major characteristics of pilomatricomas. The pilomatricomas could be categorized into five types, with type II having a diagnostic performance of sensitivity of 65.08%, specificity of 98.95%, area under the receiver operating characteristic curve (AUC) of 0.743, positive predictive value of 97.62%, and negative predictive value of 81.03% for the diagnosis of the aforementioned skin diseases. CONCLUSION: A combination of dominantly markedly hyperechoic or hyperechoic appearance, posterior acoustic shadowing, and the presence of vascularity exhibits higher diagnostic performance for the differential diagnosis of pilomatricomas, epidermoid cysts, and dermatofibrosarcoma protuberans.

Disease-Specific Mortality of Dermatofibrosarcoma Protuberans After Mohs Surgery Versus Wide Local Excision: A Systematic Review and Meta-Analysis.

BACKGROUND: Although advances have been made in the understanding of recurrence patterns in dermatofibrosarcoma protuberans, the current understanding of disease-specific mortality after surgical management is limited. OBJECTIVE: To understand disease-specific mortality rates associated with dermatofibrosarcoma protuberans treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS). MATERIALS AND METHODS: A systematic literature search was conducted on March 6, 2023, to identify patients treated with MMS or WLE for dermatofibrosarcoma protuberans. RESULTS: A total of 136 studies met inclusion criteria. Overall, the disease-specific mortality rate was not significantly different after treatment with MMS (0.7%, confidence interval [CI] 0.1-1.2, p : 0.016) versus WLE (0.9%, CI 0.6-1.2, p < .001). For recurrent tumors, the MMS treatment group had a statistically significantly lower disease-specific mortality rate (1.0%, CI 0.0-2.0, p 0.046) compared with the WLE treatment group (3.5%, CI 2.0-5.1, p < .001). The mean follow-up for all studies was 57.6 months. CONCLUSION AND RELEVANCE: The authors' meta-analysis suggests there is no substantial difference in disease-specific mortality between MMS and WLE in patients with dermatofibrosarcoma protuberans, except in the case of recurrent tumors, where MMS seems to confer a survival advantage.

Subtotal Thigh Flap for Large Abdominal Wall Defect Reconstruction in Patient With Recurrent Dermatofibrosarcoma Protuberans: A Case Report and Literature Review.

BACKGROUND: Harvesting an adequate-sized flap is challenging for reconstructing large defects on the abdominal wall. A subtotal thigh flap would be one of the choices as it provides a well-vascularized large flap with muscle components. Moreover, dermatofibrosarcoma protuberans (DFSP) is a low-grade dermal neoplasm with a high recurrence rate. There is still no consensus on the extent of resection to prevent a recurrence. OBJECTIVES: We present a case of a patient who underwent the reconstruction of a large abdominal wall defect with a subtotal thigh flap after the resection of recurrent DFSP. MATERIALS AND METHODS: A 59-year-old man killed from a recurrent huge mass in the lower abdomen with an invasion of the small intestine. His baseline characteristics and records of operations, medications, and outcomes were reviewed. RESULT: After tumor excision, a 28 × 30-cm subtotal thigh flap was harvested from his left thigh to reconstruct the abdominal defect. A microvascular anastomosis with left deep inferior epigastric vessels was made eventually. The flap was in good condition, and the donor site was covered with a split-thickness skin graft. CONCLUSIONS: Subtotal thigh flap may be considered for large abdominal wall defect reconstruction as it allows good perfusion of relatively large skin paddles compared with other free flaps. Also, patients with DFSP need definite margin-free resection and close follow-up to prevent a recurrence.

Dermatofibrosarcoma Protuberans in "Slow Mohs-tion": Multidisciplinary Approach of A Pediatric Dermatofibrosarcoma Protuberans of the Scalp with Slow Mohs Micrographic Surgery and A Double Rotational-Advancement Scalp Flap.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft-tissue sarcoma with primary incidence of 4.1 per million person-years and accounts for 0.1% of all malignancies. In patients under the age of 19, DFSP comprises 6% of cases with an annual incidence of 1 in 1,000,000. It is a slow-growing malignancy with low metastatic potential. However, DFSP is notable for its high rates of local recurrence due to local invasion with its classic "finger-like" projections into normal tissue. We discuss a case of dermatofibrosarcoma protuberans on the scalp of a 14-year-old male with delayed diagnosis, which required extensive resection through slow Mohs Micrographic Surgery (sMMS). This resection created a sizeable scalp defect of nearly 100 cm 2 , which mandated creative reconstruction using a novel double rotational-advancement scalp flap to close the defect while maintaining the patient's hairline for optimal cosmesis.

[Fascio-cutaneous exeresis of a dermatofibrosarcoma of Darier-Ferrand of the right flank]. / Exérèse fascio-cutanée d'un dermatofibrosarcome de Darier-Ferrand du flanc droit.

INTRODUCTION: Darrier-Ferrand dermatofibrosarcoma (DFSC) is the most common cutaneous sarcoma. It generally affects subjects with an average age of 40 years, without gender or race predominance. It is a tumour characterised by a slow evolution and local aggressiveness. The reasons for consultation are pain, pruritus or rapidly progressive evolution. There are no specific imaging studies for this tumour. The diagnosis of certainty is based on immunohistochemistry with positive CD34 labelling. Treatment is surgical based on wide excision. MATERIAL AND METHODS: This is an observation of a patient operated in our department for the initial diagnosis of cutaneous leiomyosarcoma of the right flank that rapidly increased in volume to 10cm in six months. A large fasciocutaneous excision was performed. The postoperative course was simple. DISCUSSION: In our patient, this lesion occurred on an old burn scar. This notion of skin trauma preceding the appearance of DFSC is reported in 10 to 20% of cases. The rapid increase in volume was the reason for consultation. The diagnosis of DFSC could only be made on definitive analysis of the surgical specimen, which showed positive immunostaining for CD34. The occurrence of metastases, although rare, confers a survival of no more than two years. The prognostic factors depend on the quality of the surgical excision, the presence of metastases and certain locations (head, neck), which make the surgery particularly mutilating. Only long-term monitoring attests to definitive cure, given the frequency of recurrence. CONCLUSION: DFSC is a rare and slowly evolving tumour. Wide surgical excision should be attempted in most cases. In inoperable cases, the use of targeted therapies (IMATINIB) has led to complete cures in some cases.

Novel role of fluorescent in situ hybridization technique (FISH) in recommended surgical margins of dermatofibrosarcoma protuberans: A preliminary study.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare skin tumor. There is no standard recommendation for its surgical management. The currently used histological analysis are HES (hematoxylin eosin saffron) staining and immunohistochemistry for CD34 expression in particular cases. Fluorescent in situ hybridization (FISH) technique is only used to qualify the DFSP as translocated or non-translocated and is not used as a diagnostic method. The aim of our study was to determine by FISH (as a diagnostic method) whether cancerous cells that could not be identified through HES staining±immunohistochemistry were present at the two-centimeter margins that were found to be tumor-free. METHODS: Samples from patients who underwent surgery between 2010 and 2018 were collected. Intralesional and peripheral (at 2cm margins) paraffin slides were included. An average of 7.4 slides per specimen was analyzed. Firstly, the preselected slides were reread by a senior pathologist to confirm the absence of microscopic findings of DFSP at 2cm margins. Secondly a FISH analysis was used as a quantitative diagnostic approach, in order to find the t(17;22) translocation. RESULTS: Among the seven specimens that included 2cm margins, two samples presented one or more translocations, which were not visible in standard morphology assessments at two centimeters tumor-free margins. CONCLUSIONS: FISH analysis can have a new role in defining tumor-free margins. This would reduce the incidence of disease recurrence after resection and improve the post-operative complementary care.

Review on the Role of Paraffin-embedded Margin-controlled Mohs Micrographic Surgery to Treat Skin Tumors. / [Artículo traducido] Revisión del rol de la cirugía micrográfica con cortes en parafina en el tratamiento de tumores cutáneos.

Paraffin-embedded margin-controlled Mohs micrographic surgery (PMMS) includes various procedures such as slow Mohs or deferred Mohs technique, the Muffin and Tübingen techniques, and staged margin excision, or the spaghetti technique. PMMS is a variation of conventional Mohs micrographic surgery (MMS) that allows histopathological examination with delayed margin control. PMMS requires minimum training and may be adopted by any hospital. The setback is that PMMS can require procedures across multiple days. PMMS lowers the rate of recurrence of basal cell carcinoma vs wide local excision in high-risk basal cell carcinoma, and improves the rates of recurrence and survival in lentigo maligna. PMMS can be very useful in high-risk squamous cell carcinoma treatment. Finally, it is a promising technique to treat infrequent skin neoplasms, such as dermatofibrosarcoma protuberans, or extramammary Paget's disease, among others. In this article, we present a literature narrative review on PMMS, describing techniques and indications, and highlighting long-term outcomes.

Review on the Role of Paraffin-embedded Margin-controlled Mohs Micrographic Surgery to Treat Skin Tumors.

Paraffin-embedded margin-controlled Mohs micrographic surgery (PMMS) includes various procedures such as slow Mohs or deferred Mohs technique, the Muffin and Tübingen techniques, and staged margin excision, or the spaghetti technique. PMMS is a variation of conventional Mohs micrographic surgery (MMS) that allows histopathological examination with delayed margin control. PMMS requires minimum training and may be adopted by any hospital. The setback is that PMMS can require procedures across multiple days. PMMS lowers the rate of recurrence of basal cell carcinoma vs wide local excision in high-risk basal cell carcinoma, and improves the rates of recurrence and survival in lentigo maligna. PMMS can be very useful in high-risk squamous cell carcinoma treatment. Finally, it is a promising technique to treat infrequent skin neoplasms, such as dermatofibrosarcoma protuberans, or extramammary Paget's disease, among others. In this article, we present a literature narrative review on PMMS, describing techniques and indications, and highlighting long-term outcomes.

Unraveling intratumoral complexity in metastatic dermatofibrosarcoma protuberans through single-cell RNA sequencing analysis.

Dermatofibrosarcoma protuberans (DFSP) stands as a rare and locally aggressive soft tissue tumor, characterized by intricated molecular alterations. The imperative to unravel the complexities of intratumor heterogeneity underscores effective clinical management. Herein, we harnessed single-cell RNA sequencing (scRNA-seq) to conduct a comprehensive analysis encompassing samples from primary sites, satellite foci, and lymph node metastases. Rigorous preprocessing of raw scRNA-seq data ensued, and employing t-distributed stochastic neighbor embedding (tSNE) analysis, we unveiled seven major cell populations and fifteen distinct subpopulations. Malignant cell subpopulations were delineated using infercnv for copy number variation calculations. Functional and metabolic variations of diverse malignant cell populations across samples were deciphered utilizing GSVA and the scMetabolism R packages. Additionally, the exploration of differentiation trajectories within diverse fibroblast subpopulations was orchestrated through pseudotime trajectory analyses employing CytoTRACE and Monocle2, and further bolstered by GO analyses to elucidate the functional disparities across distinct differentiation states. In parallel, we segmented the cellular components of the immune microenvironment and verified the presence of SPP1+ macrophage, which constituted the major constituent in lymph node metastases. Remarkably, the CellChat facilitated a comprehensive intercellular communication analysis. This study culminates in an all-encompassing single-cell transcriptome atlas, propounding novel insights into the multifaceted nature of intratumor heterogeneity and fundamental molecular mechanisms propelling metastatic DFSP.

Outcome After Surgical Treatment of Dermatofibrosarcoma Protuberans (DFSP): Does it Require Extensive Follow-up and What is an Adequate Resection Margin?

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumour of indeterminate malignant potential. The mainstay treatment for DFSP is surgical resection. Given the reported high local recurrence rate, the ideal resection margin for DFSP is unclear. The purpose of this study was to ascertain the local recurrence and metastatic rate of DFSP and DFSP with fibrosarcomatous degeneration (FS-DFSP), with specific attention to margin status in an attempt to address the issue of margin adequacy. METHODS: Patients treated for DFSP at a single sarcoma centre were identified from a prospective database. DFSP and FS-DFSP patients with and without prior surgery were included. Patients were followed after surgery to monitor complications, local recurrence and metastasis. RESULTS: The study included 200 patients: 166 patients with DFSP and 34 patients with FS-DFSP. In the DFSP group, nine patients (5.4%) had positive margins, one case (0.6%) developed local recurrence (LR) and no patients developed distant metastases. In the FS-DFSP group, seven patients (20.6%) had positive margins, six patients (17.6%) developed local recurrence (LR) and eight patients (23.5%) developed distant metastases, of which three (37.5%) were in the lungs, one (12.5%) in bone and four (50%) in other soft tissue sites. DISCUSSION AND CONCLUSION: Local recurrence and metastases are extremely rare in patients with DFSP. Achieving a negative as opposed to a wide surgical margin may be sufficient to avoid local recurrence of most DFSP. We suggest that no ongoing surveillance for local or systemic relapse is required for DFSP patients after negative margin resection. For FS-DFSP, we recommend the same surveillance schedule, based on tumour grade, as other soft tissue sarcoma.